渐冻人-ALS novel gene discovery (转载)
ALS Ice Bucket Challenge fuels novel gene discovery
Written by Honor Whiteman
Published: Thursday 28 July 2016 Published: Thu 28 Jul 2016
Muscular Dystrophy / ALS
Genetics Neurology / Neuroscience Clinical Trials / Drug Trials
In the summer of 2014, the ALS Ice Bucket Challenge took the world by storm; social media was teeming with videos of celebrities and members of the general public tipping buckets of ice water over their heads, in order to raise money for research into amyotrophic lateral sclerosis. Now, it seems the charity campaign has paid off; it has enabled the discovery of a gene that contributes to development of the neurodegenerative disease.
In a study published in the journal Nature Genetics, co-lead investigator John Landers, Ph.D., of the University of Massachusetts Medical School, and his team reveal how mutations in a gene called NEK1 increase susceptibility to amyotrophic lateral sclerosis (ALS).
The researchers say their study - which was funded by the ALS Association through donations raised by the Ice Bucket Challenge - represents a major step toward eradicating the disease once and for all.
ALS, also known as Lou Gehrig's disease, is a condition triggered by death or degeneration of nerve cells in the brain and spinal cord that are responsible for muscle control.
According to the ALS Association, around 15 people in the United States are diagnosed with ALS each day, and as many as 30,000 Americans are currently living with the condition.
Around 90-95 percent of ALS cases are sporadic, while around 5-10 percent of cases are familial, caused by inherited mutations in one or more genes.
Early symptoms of ALS include muscle twitching, tightness, and stiffness, muscle weakness in an arm or leg, slurred speech, and problems chewing or swallowing.
As the disease progresses, muscle weakness spreads to other parts of the body, making everyday tasks - such as buttoning a shirt or turning a key - challenging. Eventually, the condition causes paralysis, and in the later stages, the breathing muscles may be affected.
The prognosis for ALS patients is poor; the average life expectancy after an ALS diagnosis is 2-5 years, highlighting a crucial need to identify a cure for the disease. The novel gene discovery from Dr. Landers and colleagues may have brought us closer to finding one.
NEK1 mutations contribute to both sporadic, familial ALS
The new study forms a part of Project MinE, an international collaboration that aims to increase understanding of the genetic basis of ALS.
To reach their findings, the researchers used whole-exome sequencing to analyze genes present in 1,022 familial cases of ALS, and they compared these with the genes of 7,315 families without the condition.
From this, they uncovered a link between mutations in the NEK1 gene and the presence of familial ALS, suggesting such mutations increase susceptibility to the disease.
The researchers then applied whole-exome sequencing to more than 13,000 cases of sporadic ALS, alongside another control group. They found that the NEK1 gene mutations were also present in sporadic ALS cases, suggesting they also contribute to the development of the non-familial form of the disease.
"ALS patients carried several types of mutations on the NEK1 gene," notes co-lead investigator Prof. Jan Veldink, of University Medical Centre Utrecht, the Netherlands. "The risk of ALS might vary for these various mutations. But it is clear that this NEK1 gene is an important step forward in our search for the genetic causes of ALS."
ALS Ice Bucket Challenge crucial to new discovery
The researchers and the ALS Association stress that this major discovery would not have been possible without donations raised from the ALS Ice Bucket Challenge.
"The ALS Ice Bucket Challenge enabled The ALS Association to invest in Project MinE's work to create large biorepositories of ALS biosamples that are designed to allow exactly this kind of research and to produce exactly this kind of result," says Lucie Bruijn, Ph.D. chief scientist at the ALS Association.
This will be welcome news for many, since the charity campaign was largely criticized at the time. Despite clocking up around $115 million in donations, the campaign was penned by some as promoting "slacktivism" - that is, the act of showing support, possibly to boost one's ego, without providing a donation.
What is more, the ALS Association was chastised after an article went viral that claimed to show documents proving 73 percent of donations to the charity are not used for research purposes. The claims were debunked.
"The ALS Ice Bucket Challenge enabled us to secure funding from new sources in new parts of the world. Thankfully, The ALS Association brought Project MinE to the United States.
This transatlantic collaboration supports our global gene hunt to identify the genetic drivers of ALS. I'm incredibly pleased with the discovery of the NEK1 gene adding another step towards our ultimate goal, eradicating this disease from the face of the earth."
Bernard Muller, Project MinE